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Late life depression and incident activity limitations:
influence of gender and symptom severity.
Isabelle Carrière, Laure-Anne Gutierrez, Karine Pérès, Claudine Berr, Pascale
Barberger-Gateau, Karen Ritchie, Marie-Laure Ancelin
To cite this version:
Isabelle Carrière, Laure-Anne Gutierrez, Karine Pérès, Claudine Berr, Pascale Barberger-Gateau, et al.. Late life depression and incident activity limitations: influence of gender and symptom sever-ity.. Journal of Affective Disorders, Elsevier, 2011, 133 (1-2), pp.42-50. �10.1016/j.jad.2011.03.020�. �inserm-00590366�
Late life depression and incident activity limitations: influence of gender and symptom
severity.
Isabelle Carrièrea,b,* PhD, Laure Anne Gutierreza,b MSc, Karine Pérèsc,d PhD, Claudine Berra,b PhD, Pascale Barberger-Gateauc,d PhD, Karen Ritchiea,b,e PhD, Marie Laure Ancelina,b PhD
a
Inserm, U1061, Montpellier, F-34093, France
b
University Montpellier1, Montpellier, F-34000, France
c
Inserm, U897, Bordeaux, F-33076, France
d
University Victor Segalen Bordeaux 2, Bordeaux, F-33076, France
e
Faculty of Medicine, Imperial, College, St Mary’s Hospital, London, UK
* Corresponding Author Isabelle Carrière Inserm U1061 Hopital La Colombière, BP 34493
34093 Montpellier Cedex 5, France
Tel: +33 499 614 691
Fax: +33 499 614 579
Email: isabelle.carriere@inserm.fr
Abstract
Background
Mental disorders, especially depression, are one of the principal causes of disablement.
Previous research has been limited partly due to the failure to take into account
sub-syndromal states and the very large number of candidate mediating and confounding factors.
Methods
Longitudinal associations between baseline depressive symptomatology and activity
limitations were examined in a community-dwelling elderly cohort of 3191 participants.
Mixed logistic models were used to determine associations between mild or severe depressive
symptoms (Center for Epidemiologic Studies-Depression Scale, CES-D), and 7-year incident
disability on four limitation scales assessing instrumental and basic activities of daily living,
mobility using the Rosow and Breslau scale, and social restriction.
Results
In men, mild depressive symptomatology was associated with increased incident limitations
on instrumental activities of daily living (IADL) (odds ratio (OR)
(95%CI)=5.07(2.25-11.42)). In women, severe depressive symptomatology was related to social restriction
(OR(95%CI)=2.36(1.31-4.25)), IADL (OR(95%CI)=1.89(1.13-3.15)) and activities of daily
living (OR(95%CI)=11.15(3.43-36.23)). Men and women with a 2-year increase in CES-D
score were highly at risk for social restriction and limitations in mobility and IADL.
Conclusion
Depression is an independent predictor of disability in the elderly population; the relation is
gender-dependent and varies with symptom load.
Key words: Aged; Longitudinal studies; Disability evaluation; Depression; Gender
Introduction
Mental disorders are one of the principal causes of disablement; the Global Burden of Disease
reporting that neuropsychiatric conditions account for up to a quarter of all
Disability-Adjusted Life-Years (DALYs) (Murray and Lopez, 1996; Prince et al., 2007). Depression in
particular is associated with high mortality and disability, accounting for 4.46% of DALYs
and 12.1% Years of Life with Disability (YLDs) (Ustun et al., 2004). It is above all late life
depression which significantly reduces disability-free life expectancy (Peres et al., 2008).
Estimates of the life-time prevalence of major depression in elderly cohorts vary widely (3 to
19%) (Lyness et al., 1999; Ritchie et al., 2004), this variability being largely attributable to
assessment methods (clinical/standardised examination/self-evaluation) and the type of
depression investigated (major, minor or depressive symptoms). Most elderly people who
have clinically significant depressive symptoms do not meet the full diagnostic criteria for
major depression (Blazer, 2003; Rollman and Reynolds, 1999), however, sub-syndromal
depression has both a high prevalence in later life and poor response to anti-depressant
treatment (Kirsch et al., 2008). It may thus constitute a major cause of disability for which
treatment methods are presently unsatisfactory.
A better understanding of the association between both major and sub-syndromal depression
and disability constitutes an important first step in identifying alternative intervention points
for therapeutic intervention. Previous research has been limited not only due to failure to take
into account sub-syndromal states and the very large number of candidate mediating and
confounding factors, but also the inadequacy of the disability measures used. Previous
longitudinal studies have principally used partial dependency measures incorporating different
items from activities of daily living (ADL) or instrumental activities of daily living (IADL)
scales (Carriere et al., 2009; Schillerstrom et al., 2008). Furthermore, although gender
depression, differential susceptibility to depression-related disability has surprisingly seldom
been investigated. We recently reported that the association between depression and 4-year
mortality is dependent both on gender and disease severity, the greatest risk being observed
for men with severe depression (Ryan et al., 2008).
The purpose of this study is to examine the long-term association between depressive
symptoms and incident activity limitations in a large elderly prospective community cohort,
for which information on a large number of potential confounding factors was available. The
analyses are based on four independent scales of activity limitation corresponding to different
METHOD Study sample
Subjects were recruited as part of a multi-site cohort study of community-dwelling persons
aged 65 years and over from the electoral rolls of three French cities (Bordeaux, Dijon and
Montpellier) between 1999 and 2001 (The 3C Study Group, 2003). The study protocol was
approved by the Ethical Committee of the University-Hospital of Bicêtre (France) and written
informed consent was obtained from each participant. A standardized evaluation with a face
to face interview and a number of clinical examinations was undertaken in the three study
centres at baseline, 2 and 4 years. In the centres of Bordeaux and Montpellier this follow-up
was extended with an examination at 7 years.Of the 4215 dementia-free participants included
in these two centres, 408 were missing all follow-up evaluations for activity limitations (of
whom 170 died) and 616 had missing data for at least one baseline adjustment variable. The
present analyses were thus conducted on 3191 subjects (1617 from Bordeaux and 1574 from
Montpellier; 1311 men and 1880 women).
Compared with the analysed sample, those not included in this analysis were more likely
to be older (p < 0.0001), have lower education (p<0.0001), be more depressed (p< 0.0001),
use antidepressants (p=0.004), live alone (p=0.02) and have disabilities (p<0.0001), cognitive
impairment (p<0.0001), comorbidity (p<0.0001), visual impairment (p=0.03) and hearing
impairment (p<0.0001).
Disability measures
Three complementary measurements of activity limitations were investigated as outcomes:
mobility, complex or instrumental activities of daily living (IADLs) and basic activities of
daily living (ADLs). Mobility was assessed according to the Rosow and Breslau scale (Rosow
and Breslau, 1966) which evaluates ability to do heavy housework, walk half a mile, and
telephone, to manage medication and money, to use public or private transport, to shop, and
for women only, to prepare meals and do housework and laundry (Lawton and Brody, 1969).
For ADLs, participants were asked whether they needed help for any task on the Katz ADL
scale: bathing, dressing, transferring from bed to chair, toileting, and eating (incontinence was
not considered since it reflects organ impairment rather than functional limitation) (Katz et al.,
1970). For each domain of disability, participants indicating inability to perform one or more
activities without help were considered as having mobility, IADL, or ADL limitations. A
fourth outcome was social restriction (confinement to bed, home or outings restricted to
neighbourhood) which can be considered as participation restriction according to the
International Classification of Functioning, Disability, and Health (ICF, 2001 ).
Depression
The Mini International Neuropsychiatric Interview (MINI) (Sheehan et al., 1998), a
standardised psychiatric examination which has been validated in the general population, was
used for the diagnosis of current and past major depressive episodes (MDE), according to
DSM–IV criteria. Severity of depressive symptoms was assessed using the 20-item Center for
Epidemiologic Studies–Depression scale (CES–D) (Radloff, 1977). For this analysis,
participants were classified into one of three groups (Ryan et al., 2008). 'Severe depressive
symptomatology' (Severe DS group) included participants with a current MDE or a CES–D
score of 23 or over (allowing for the fact that some participants with severe symptoms did not
reach DSM classification criteria, principally because of the duration of symptoms). 'Mild
depressive symptomatology' (Mild DS group) was defined as a CES–D score between 16 and
22 and 'no DS' included participants with a CES–D score lower than 16. Deterioration in
depressive symptoms between inclusion and the first follow-up examination was defined as
validated by presentation of the prescription or medication to the interviewer, and type of medication was noted according to the World Health Organization’s Anatomical Therapeutic Chemical (ATC) classification.
Socio-demographic and clinical variables
The standardized interview included questions on demographic characteristics, education
level (classified in four groups corresponding to 5, 9, 12, and 12+ years of education), marital
status, income, mode of living (alone or not), height, and weight. Information was obtained on
type and quantity of alcohol consumption (number of units of alcohol per day; 0, 1-36, >36
g/day), tobacco use (classified as past, present or never users) as well as use of hormonal
therapy (HT) (never, past, current use) for women. Detailed medical questionnaires included
history of stroke, angina pectoris, myocardial infarction, and cardio-vascular surgery
established according to standardized questions, history of cancer and fracture with
hospitalisation during the last two years, asthma (attacks during the last year), chronic
bronchitis, dyspnoea, hypertension (>160/95 mm Hg or treated), diabetes (fasting glycemia>
7mmol/l or treated) and thyroid disease. Blood pressure was measured during the interview
using a digital electronic tensiometer OMRON M4. The number of chronic diseases was
calculated including: hypertension, diabetes, cardiovascular diseases, respiratory diseases,
dyspnoea, thyroid disease, and cancer.
Cognitive impairment was defined as a Mini Mental State Examination (MMSE) (Folstein et
al., 1975) score lower than 24. Visual impairment was defined as having a corrected near
visual acuity (Parinaud scale) of less than 4 or difficulties recognizing a familiar face at 4
meters. Hearing impairment was defined deafness or only able to hear a conversation when a
Statistical analyses
Separate analyses were conducted for men and women. The Chi2 test was used to
identify gender-related differences. For each indicator of activity limitations longitudinal
associations with the levels of DS were established from subjects free of that activity
limitation at baseline. Thus the sample size was 951 men and 954 women for mobility, 1245
men, and 1723 women for IADL, 1303 men and 1864 women for ADL and 1276 men and
1738 women for social restriction.
In longitudinal studies, the within-subject responses (repeated evaluations of activity
limitations) are correlated. This correlation was accounted for by using a mixed logistic model
(Carriere and Bouyer, 2002). Briefly, this model has four basic characteristics: (i) the
individual time evolutions of activity limitations are entirely taken into account including
possible reversion to normal state (ii) subjects with incomplete responses across time are
included in the analysis; (iii) subjects do not have to be evaluated at the same time points; (iv)
the model allows within-subjects dependency to vary from one subject to another, via the
random part of the covariable linear combination. The SAS procedure NLMIXED was used to
estimate the parameters (version 9.1).
We used univariate and multivariate models to determine if baseline DS was associated
with odds of activity limitations or social restriction during follow up. After gender
stratification, univariate odds ratios were adjusted for centre, age, time and interaction
time*age (Model 0). Multivariate adjusted logistic regression included covariates that were
associated with the follow-up responses (p<0.15 in univariate model). Model 1 was adjusted
for age, centre, time, time*age, alcohol, body mass index (BMI), smoking, number of chronic
pathologies, cognitive impairment, visual impairment, hearing impairment and HT (women
only). Model 2 was further adjusted for income, education level and living alone and Model 3
A sensitivity analysis was also performed. The non-respondents at 7 years were contacted by
telephone and invited to answer a short questionnaire exploring medication use, activity
restrictions (ADL, IADL, mobility), cognitive performances (MMSE, verbal fluency test) and
depressive symptoms (CES-D). Information obtained by telephone were pooled with the
study data base in order to examine potential bias due to non random loss to follow-up.
RESULTS
Within this elderly community-dwelling sample, the baseline prevalence of Severe DS (major
depressive disorder or CES-D ≥ 23) was 11.8% and that of Mild DS (CES-D 16-22) was
9.2%. Past MDE was reported by 40.3% of subjects with Severe DS and 20.5% with Mild DS
and the mean age (SD) of first episode onset was 43.9 (16.1) years. Women had a
significantly higher prevalence of Severe and Mild DS than men, were more often treated
with antidepressants, and declared more frequently a history of MDE (Table 1).
For every baseline disability scale except ADL, women reported activity limitations
significantly more frequently than men (7.50% vs 2.52% for social restriction, 48.63% vs
26.45% for mobility, and 7.96% vs 4.59% for IADL). Compared to men, women were also
less educated, more likely to live alone, have a lower incomes more visual and cognitive
impairment but were less likely to have hearing impairment, comorbidity, to be overweight or
obese, to smoke and take alcohol.
The analysis of the repeated activity limitation proportions was undertaken for each scale on
the subjects without limitation on the considered scale at baseline. Table 2 shows the rates of
activity limitations over 7 years in men and women according to the level of baseline DS and
the odds ratios of having incident activity limitations adjusted for age, centre, time and the
interaction between time and age (model 0). Over the follow-up period, the probability of
becoming disabled tended to increase for all the indicators and whatever the level of DS. All
that the effect of time on activity limitations was more pronounced in the oldest old. For ADL
in men time and age were significant, but not the interaction.
Compared with men without DS at baseline, the risk of having IADL limitations during
follow-up was highly significantly greater in men with Mild DS (OR(95%CI)=5.20
(2.37-11.38)) (Table 2). This association was also significant for social restriction
(OR(95%CI)=2.71 (1.01-7.26)) and mobility (OR(95%CI)=1.87(1.00-3.50)). In women
whatever the outcome scale, baseline Mild DS was not found to be significantly related to the
odds of activity limitations during follow-up. Baseline Severe DS was only found to be
significant in men for social restriction (OR(95%CI)=3.85(1.05-14.04)) while in women it
was highly significant for social restriction (OR(95%CI)=3.57(1.93-6.61)), IADL
(OR(95%CI)=2.47(1.48-4.11)) and ADL (OR(95%CI)=13.29(4.50-39.31)).
When the mixed logistic models were further adjusted for possible confounding factors
(model 3) all the preceding associations persisted except in men for social restriction and
mobility. In men (Table 3), Mild DS was highly significantly associated with the adjusted
odds of IADL limitations (OR(95%CI)=5.07(2.25-11.42)) while in women (Table 4) Severe
DS was related to social restriction (OR(95%CI)=2.36(1.31-4.25)), IADL (OR(95%CI)=1.89
(1.13-3.15)) and ADL limitations (OR(95%CI)=11.15(3.43-36.23)). The multi-adjusted OR
values tended to slightly decrease when covariates linked to medical burden were added to the
model (model 1) as well as when past MDE and antidepressant use were further included
(model 3) but not when socioeconomic status was added (model 2).
These results were not modified when the data from the phone interview were added as a
sensitivity analysis to test the potential bias due to non-random dropout (321 additional time
points at 7 years). The associations found in model 3 also remained significant when
excluding the case of incident dementia (130 women and 78 men) except for severe DS and
associated with IADL limitations (OR(95%CI)=4.31(1.85-10.06)) and in women Severe DS
was still associated with social restriction (OR(95%CI)=1.99(1.04-3.80)) and ADL limitations
(OR(95%CI)=7.47(1.81-30.84)).
No interactions were found between DS (mild or severe) and centre, past MDE or the number
of chronic pathologies or cognitive, visual or hearing impairments, except in women for social
restriction (p-value for interaction=0.04); depressed women with hearing impairment being at
higher risk of confinement to home or neighbourhood (n=53, p=0.03) whereas the association
with DS was not significant in those who were not hearing impaired (n=1685, p=0.42).
Among the 2377 subjects (1070 men and 1307 women) free of DS and of disability at
baseline and with a 2-year depression evaluation, 27.1% of the men and 34.3% of the women
had an increase in the CES-D score of at least three points over the first two years (χ2 test, p=0.0002). The odds of having activity limitations associated with a 2-year increase in CES-D
score was significantly higher in men and women for social restriction, mobility and IADL
(Table 5). These associations were especially strong in men for social restriction and IADL
DISCUSSION
Gender differences in depression-related activity limitation risk
The most striking findings of this large study of community-dwelling elderly were that
activity limitations risk varied according to DS severity and by sex. Women with Mild DS did
not show increased risk in relation to any disability type, but those with severe DS were at
higher risk of limitations in IADL, ADL and social restriction. On the other hand, men with
Mild DS were at high risk of IADL limitations; an increased risk in social and mobility
restriction was also found in an age-adjusted model, but this failed to reach significance in the
multi-adjusted models. In men with Severe DS, we did not observe a significant association
with any of the disability measures after 7 years of follow-up, probably due to lower number
(4.9% compared to 12.2% for women) and a higher mortality rate. Indeed in the same cohort,
an increase in depression-related 4-year mortality risk was observed in men with mild
(OR=2.8) and treated severe DS (OR=5.3) whereas in women only non-treated severe DS
which slightly increased risk (OR=1.8) (Ryan et al., 2008).
Several previous studies have reported an increase in activity limitations (most frequently
severe ADL limitations) associated with DS in elderly community cohorts (see (Carriere et
al., 2009; Schillerstrom et al., 2008), for reviews). Only two prospective studies have
examined the impact of gender differences on severe level of disability (Barry et al., 2009;
Dalle Carbonare et al., 2009). Dalle Carbonare et al observed an association between DS and
short-term limitations in ADL for both gender and physical function disability for men (Dalle
Carbonare et al., 2009). Barry et al using a 4-item ADL scale found an increased risk of
experiencing severe disability associated with moderate and high levels of DS in men, and
only with severe DS in women (Barry et al., 2009). We also observed an association between
significant only in age-adjusted but not multi-adjusted model, probably due to a lack of
power; few people being severely disabled in our sample.
Disability in relation to depression severity and gender differences
Our study is, we believe, the first to use several activity limitation scales in their validated
forms. Mobility, IADL and ADL limitations correspond to an increased gradient of severity
(Barberger-Gateau et al., 2000). Severe DS was predictive of multiple disabilities in women
whereas the more likely consequence in men would be on mortality. Whereas ADL appears as an “ultimate” indicator of disability associated with Severe DS, IADL appears to be a more sensitive marker of disability as a function of depression severity level in our sample. Men
with Mild DS were at very high risk of IADL disability (OR=5.07) whereas women even with
Severe DS were at lower risk (OR=1.89). On the other hand, mobility limitations which
correspond to a lower level of disability are probably not sufficiently sensitive to DS in this
elderly sample (39.5% with such activity limitations at baseline). Mobility limitations were
observed in people without DS at baseline but showing an early slight deterioration in CES-D
score during follow-up. This was also the case for social restriction and IADL. We observed a
slight gender difference in mobility and social restriction and a notable difference in IADL,
men being at higher risk of disability. Our study thus gives an indication of the dynamics of
the evolution of activity limitations at increasing levels of DS severity; different patterns of
disability evolution possibly explaining gender differences. Some authors have distinguished
subjects who rapidly develop severe disability (in less than one year - also called catastrophic
disability) from those who develop severe disability for a longer period (progressive or
insidious disability) (Ferrucci et al., 1996; Gill et al., 2004; Gill et al., 2010). Catastrophic
disability could be the consequence of precipitating events such as stroke, hip fracture, cancer
aggregate of subclinical losses of reserve across multiple physiologic systems (Bortz, 2002;
Fried et al., 2001) or insidious onset of cognitive deterioration. Both time spent in disability
and time before death are shorter in men (Deeg et al., 2002; Peres and Jagger, 2005)
indicating that men may be more vulnerable to catastrophic disability whereas women are at
greater risk of an insidious progression with longer time spent in states of severe disability.
Our results suggest that moderate DS could contribute to more rapid disability progression in
men while in women severe DS is associated with slower progression.
Mechanisms potentially involved in the association between depression and disability
The mechanisms by which depression may generate activity limitation are not fully
understood and may involve a combination of factors including physical comorbidity,
cognitive and sensorial impairment, health behaviours, and biological factors. Vascular
comorbidity is of particular importance in this context as it has been reported to be associated
with functional decline (Wang et al., 2002). Depression could be an intermediate state
between cerebral vascular disease and disability (Alexopoulos et al., 1997; Schillerstrom et
al., 2008). We however, controlled for hypertension, diabetes, stroke, and cardiovascular
disease and the association remained significant, suggesting that this pathway does not fully
explain the association.
The early symptoms of cognitive decline are often destabilising and may also induce a
depressive state. Inversely depression is associated with apathy and impaired cognitive
functioning. The relationships persisted even after adjusting for baseline cognitive level and
there was no significant interaction between cognitive impairment and depression in our
study. Mehta et al (Mehta et al., 2002) found that in elderly people without ADL limitations,
risk factors for functional decline. In a sample of vulnerable elders eligible for nursing home
care, Li et al (Li and Conwell, 2009) found that cognitive decline was associated with more
elevated IADL scores when depression status worsened, but this was not observed for ADL
scores. The strength of the interaction between DS and cognition probably depends on both
cognitive level and degree of disability within the study population. A relatively small
proportion of the participants in our study were at high risk for dementia (4.2% had baseline
MMSE <24) which may explain the lack of interaction.
Sensory impairments, have been demonstrated to be a predictor of both onset and persistence
of depression and functional disability (Chou, 2008; Crews and Campbell, 2004; Owsley et
al., 2007). In our analysis, the relationship persisted after adjustment for both visual and
hearing impairment. However, the assessment of hearing impairment was self-reported and
the adjustment may not be complete considering that sensory impairments are often
unrecognized by elderly people due to their slow progression.
Several behavioural mechanisms could also explain the disability risk associated with
depression including impaired motivation and lower treatment compliance (Ciechanowski et
al., 2000; Vinkers et al., 2004). Men in particular are likely to behave in ways which are
detrimental to their overall health (Ciechanowski et al., 2000), however, the associations
persisted even after controlling for comorbidity and “self-care” variables (i.e. smoking,
alcohol, BMI, and level of visual and hearing impairment). More subjective factors such as
impairment in affect regulation, social perception and greater tendency to amplify physical
symptoms (Ormel et al., 1994) may also have played a role. Finally, dysfunctioning in the
hypothalamic-pituitary-adrenal and sympathetic axes and immune system may also be
Limitations
The data concerning disability outcomes were self-reported which may have led to
over-reporting in depressed participants. Bias could also be introduced by the exclusion of
participants with missing baseline data or lost to follow-up, who were more likely to be
depressed, disabled or to have died. A difference in the attrition of our cohort was observed,
men with DS being more often lost to follow-up (31.4% of depressed men and 14.9% of
depressed women died during follow-up, 57.9% of depressed men and 48.5% of depressed
women had less than 4 examinations). Men with DS may thus be censored before becoming
disabled, so that associations between depression and disability were underestimated.
However, the same results were obtained when data from telephone interviews of
non-respondents were included (data not shown). Finally, in our study, we had no information
regarding level of pain and its association with depression (Lin et al., 2003) which may have
increased the risk of over-adjustment. We did, however, adjust for chronic pathologies
commonly associated with pain, and this did not modify the associations.
Strengths
Our prospective study based on a large community sample permitted a dynamic evaluation of
activity limitation with four evaluations over 7 years. We also used a number of validated
scales exploring the major components of disability corresponding to distinct levels of
disability severity. Depression was assessed using two distinct measures validated in the
general population, including a structured diagnostic interview (Radloff, 1977; Sheehan et al.,
1998), thus minimizing exposure misclassification. We were able to cover a wide range of
depression profiles, from sub-clinical symptoms to major depression, thus addressing the
problem of the varying definitions of depression in previous research. We also evaluated the
sensorial impairments, health behaviors), cognitive impairment, past MDE and antidepressant
use (with the risk of over-adjusting) which only slightly affected the results.
In conclusion, our findings suggest that the relationship between DS and incident activity
limitations in the elderly is gender-dependent and also varies according to symptom load.
Findings from this study suggest an increased risk of disability in men, even at the level of
sub-clinical depression. This also highlights the importance of early detection of depressive
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Acknowledgement
Funding: The 3C Study is conducted under a partnership agreement between Inserm, the
Victor Segalen-Bordeaux II University and Sanofi-Synthélabo. The Fondation pour la
Recherche Médicale funded the preparation and first phase of the study. The 3C-Study was
also supported by the Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale
de la Santé, MGEN, the Institut de la Longévité, Agence Française de Sécurité Sanitaire des
Produits de Santé, the Regional Governments of Aquitaine, Bourgogne and
Languedoc-Roussillon, the Fondation de France, the Ministry of Research-Inserm Programme 'Cohorts
and collection of biological material' and Novartis. The Lille Genopole was supported by an
unconditional grant from Eisai.
This work was carried out with the financial support of the "ANR - Agence Nationale de la
Recherche - The French National Research Agency" under the "Programme National de
Recherche en Alimentation et nutrition humaine", project "COGINUT ANR-06-PNRA-005"
and under the "Programme Longévité et vieillissement", project 07-LVIE-004" and by The
Institut de Recherche en Santé Publique (IReSP), Paris, France.
Role of funding source: the sponsors had no role in study design; in collection, analysis, and
interpretation of data; in the writing of the report; and in the decision to submit the paper for
publication.
Conflict of interest: None.
Contributors. IC: study concept, statistical analyses and drafting of the manuscript, LAG:
statistical analyses, KP, CB, PBG, KR, MLA: study concept and design, management of the
Table 1. Characteristics of the study population Men (n=1311) % Women (n=1880) % Chi2 p Age 65-69 70-74 75-80 80+ 26.77 36.92 24.26 12.05 25.64 34.36 26.70 13.30 0.21 Education ≤ 5 years 24.79 30.59 0.0003 Depressive symptomatology No Mild Severe 86.73 8.39 4.88 73.67 14.15 12.18 <0.0001
Past major depressive episode 8.54 19.57 <0.0001
Antidepressant treatment 3.66 9.15 <0.0001
Social restriction: home or neighbourhood confined
2.52 7.50 <0.0001
Activity limitations: Mobility 26.45 48.63 <0.0001
Activity limitations: IADL 4.59 7.96 0.0002
Activity limitations: ADL 0.31 0.37 0.99*
Incomes > 1500 €/month 79.56 57.55 <0.0001
Alcohol 0 1-36 g/day > 36g/day 7.40 69.79 22.81 24.73 73.30 1.97 <0.0001 Smoking Never Former Current 30.97 60.26 8.77 80.64 15.80 3.56 <0.0001 BMI Normal Overweight Obese 36.38 52.10 11.52 55.16 31.76 13.09 <0.0001
Number of chronic pathologies None 1-2 3-5 26.80 63.77 7.63 34.15 59.68 6.17 0.003 Cognitive impairment 3.13 4.95 0.01 Visual impairment 10.30 16.97 <0.0001 Hearing impairment 4.81 3.19 0.02 HRT: current 12.98
Table 2. Incident cases of disability by baseline depressive symptomatology and risk of disability adjusted for age, centre, time and time*age (model 0) Men Women Follow-up Follow-up 2 years % 4 years % 7 years % OR (95%CI)* p-value 2 years % 4 years % 7 years % OR (95%CI)* p-value
Home or neighborhood confined
Baseline DS N=1214 N=1073 N=908 N=1276 N=1650 N=1519 N=1336 N=1738
No 3.68 5.42 9.51 1 7.18 8.95 19.03 1
Mild 5.15 9.64 14.75 2.71(1.01-7.26) 0.05 5.53 10.05 16.87 1.05(0.57-1.91) 0.88
Severe 6.90 2.04 8.11 3.85(1.05-14.04) 0.04 13.64 12.58 28.15 3.57(1.93-6.61) <0.0001
Mobility: Rosow and Breslau
Baseline DS N=883 N=804 N=690 N=951 N=886 N=837 N=758 N=954
No 30.20 34.87 41.19 1 40.65 49.93 53.83 1
Mild 40.98 44.64 50.00 1.87(1.00-3.50) 0.05 45.63 61.96 42.86 1.34(0.87-2.07) 0.19
Severe 23.53 23.53 30.77 0.65(0.28-1.52) 0.32 55.56 51.52 47.27 1.45(0.88-2.39) 0.15
Baseline DS N=1179 N=1049 N=878 N=1245 N=1625 N=1502 N=1310 N=1723 No 5.25 8.55 12.60 1 6.60 13.48 20.47 1 Mild 10.31 19.32 28.13 5.20(2.37-11.38) <0.0001 10.64 13.68 20.86 1.54(0.96-2.47) 0.08 Severe 5.56 6.12 11.11 1.95(0.62-6.16) 0.26 10.67 16.05 31.30 2.47(1.48-4.11) 0.0005 ADL Baseline DS N=1234 N=1091 N=908 N=1303 N=1763 N=1621 N=1399 N=1864 No 0.75 1.58 1.61 1 0.69 1.07 2.89 1 Mild 0 3.33 6.25 3.15(0.62-15.92) 0.17 1.20 0.90 3.49 2.43(0.75-7.83) 0.14 Severe 1.69 2.00 2.63 6.55(0.84-50.88) 0.07 1.90 5.35 9.15 13.29(4.50-39.31) <0.0001 DS: Depressive Symptomatology
Table 3: Multi-adjusted associations of baseline depressive symptomatology with disability incidence in men
Model 1 Model 2 Model 3
OR (95%CI) p-value OR (95%CI) p-value OR (95%CI) p-value Home or neighborhood confined, N=1276
No DS 1 1 1
Mild DS 2.16(0.77-6.08) 0.14 2.29 (0.81-6.46) 0.12 2.22(0.80-6.13) 0.13 Severe DS 3.39(0.88-13.08) 0.08 3.57 (0.9-14.14) 0.07 2.17(0.51-9.2) 0.29 Mobility: Rosow and Breslau, N=951
No DS 1 Mild DS 1.68(0.9-3.12) 0.10 1.69 (0.91-4.49) 0.10 1.68(0.90-3.16) 0.11 Severe DS 0.6(0.26-1.39) 0.24 0.59 (0.25-1.36) 0.21 0.59(0.25-1.39) 0.23 IADL, N=1245 No DS 1 1 1 Mild DS 4.85(2.13-11.03) 0.0002 5.4 (2.38-12.24) <0.0001 5.07(2.25-11.42) <0.0001 Severe DS 1.78(0.54-5.87) 0.35 2.07 (0.62-6.94) 0.24 1.78(0.52-6.02) 0.36 ADL, N=1303 No DS 1 1 1
Mild DS 2.41(0.56-10.38) 0.24 2.16 (0.62-7.58) 0.23 2.09(0.60-7.24) 0.24 Severe DS 5.29(0.8-34.86) 0.08 4.78 (0.88-25.88) 0.07 3.82(0.68-21.39) 0.13
Model 1: adjusted for age, centre, time and time*age, alcohol, BMI, smoking, number of chronic pathologies, cognitive impairment, visual impairment, hearing impairment
Model 2: adjusted for age, centre, time and time*age, alcohol, BMI, smoking, number of chronic pathologies, cognitive impairment, visual impairment, hearing impairment, income, study level and, living alone
Model 3: adjusted for age, centre, time and time*age, alcohol, BMI, smoking, number of chronic pathologies, cognitive impairment, visual impairment, hearing impairment, income, study level, living alone, past major depressive episode and, antidepressant treatment.
Table 4: Multi-adjusted associations of baseline depressive symptomatology with disability incidence in women
Model 1 Model 2 Model 3
OR (95%CI) p-value OR (95%CI) p-value OR (95%CI) p-value Home or neighborhood confined, N=1738
No DS 1
Mild DS 0.87(0.49-1.56) 0.64 0.88 (0.5-1.56) 0.66 0.82(0.46-1.46) 0.50
Severe DS 3.01(1.68-5.41) 0.0002 2.94 (1.65-5.24) 0.0003 2.36(1.31-4.25) 0.004 Mobility: Rosow and Breslau, N=954
No DS 1 Mild DS 1.33(0.86-2.04) 0.20 1.30 (0.84-2.00) 0.23 1.27(0.82-1.97) 0.28 Severe DS 1.48(0.9-2.43) 0.12 1.44 (0.87-2.38) 0.15 1.32(0.79-2.21) 0.29 IADL, N=1723 No DS 1 Mild DS 1.26(0.79-2.00) 0.34 1.35 (0.84-2.17) 0.22 1.26(0.78-2.02) 0.34 Severe DS 2.03(1.24-3.33) 0.005 2.22 (1.34-3.67) 0.002 1.89(1.13-3.15) 0.02 ADL, N=1864
No DS 1 1 1
Mild DS 2.17(0.68-6.89) 0.19 2.23 (0.68-7.30) 0.18 2.24(0.70-7.24) 0.18
Severe DS 11.18(3.93-31.86) <.0001 12.1 (3.83-38.24) <0.0001 11.15(3.43-36.23) <0.0001
Model 1: adjusted for age, centre, time and time*age, alcohol, BMI, smoking, number of chronic pathologies, cognitive impairment, visual impairment, hearing impairment and, hormonal treatment
Model 2: adjusted for age, centre, time and time*age, , alcohol, BMI, smoking, number of chronic pathologies, cognitive impairment, visual impairment, hearing impairment, hormonal treatment, income, study level and, living alone
Model 3: adjusted for age, centre, time and time*age, alcohol, BMI, smoking, number of chronic pathologies, cognitive impairment, visual impairment, hearing impairment, hormonal treatment, income, study level, living alone, past major depressive episode and, antidepressant treatment.
Table 5: Adjusted associations of 2-year depressive deterioration (increase of 3 points or
more at CES-D) with disability incidence in subjects free of depressive symptomatology
at baseline
Men Women
OR (95%CI)* p-value OR (95%CI)* p-value
Home or neighborhood confined N=1049 N=1234
3.43 (1.72-6.86) 0.0005 2.76 (1.78-4.27) <0.0001
Mobilty: Rosow and Breslau N=794 N=725
2.18 (1.5-3.18) <0.0001 1.68 (1.2-2.35) 0.003
IADL N=1022 N=1214
3.00 (1.72-5.24) 0.0001 1.55 (1.03-2.34) 0.04
ADL N=1065 N=1300
1.64 (0.67-4.03) 0.28 2.67 (0.95-7.53) 0.06 * adjusted for age, centre, time and time*age, alcohol, BMI, smoking, number of chronic pathologies, cognitive impairment, visual impairment, hearing impairment, hormonal treatment (women only), income, study level, living alone, past major depressive episode and, antidepressant treatment.
